Phase I Study of Neoadjuvant Radiotherapy With 5-Fluorouracil for Rectal Cancer

NCT02270606 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MCC-14-10491NCI-2014-02089P30CA016059
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of fluorouracil when given together with radiation therapy followed by combination chemotherapy before and after surgery in treating patients with rectal cancer that has spread from where it started to nearby tissue or lymph nodes. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving additional combination chemotherapy after surgery may kill any remaining tumor cells. Giving radiation therapy and fluorouracil followed by combination chemotherapy before and after surgery may be a better treatment for rectal cancer.

Conditions

Mucinous Adenocarcinoma of the Rectum; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Stage IIA Rectal Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage IIIA Rectal Cancer; Stage IIIB Rectal Cancer; Stage IIIC Rectal Cancer

Keywords

Rectum

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity for continuous infusional 5-Fluorouracil given concurrently with short course pelvic radiation

  To determine the maximum tolerated dose of continuous infusional 5-Fluorouracil, up to a target dose of 200 mg/m\^2/day, given concurrently with short course radiation followed by neoadjuvant FOLFOX chemotherapy and planned surgical resection for locally advanced rectal cancer. Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.

  Up to 21 days

Secondary Outcomes (7)

• Pathological response rate for subjects treated with concurrent 5-FU

  Up to at least 5 years

• Complete response rate with radiographic imaging prior to surgery

  Up to 8 weeks after completion of pre-operative chemotherapy

• Three-year rate of local-regional recurrence for all subjects enrolled on the study

  3 years

• Adverse events at any time

  30 days after surgery

• Three-year rate of disease-free survival for all subjects enrolled on the study

  3 years

Study Arms (1)

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

EXPERIMENTAL

CHEMORADIATION:Patients undergo Intensity Modulated Radiation Therapy (IMRT) once a day over 5 days for total of 5 fractions and concurrently receive fluorouracil IV continuously over 96 hours. PREOPERATIVE CHEMOTHERAPY:Within 2 weeks of completing chemoradiation, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV as a push followed by IV continuously over 46 hours on day 1.Treatment repeats every 14 days for 4 courses in absence of disease progression or unacceptable toxicity. SURGERY:Within 4-8 weeks of completing preoperative chemotherapy, patients undergo total mesorectal excision as therapeutic conventional surgery. POSTOPERATIVE CHEMOTHERAPY:Within 4-8 weeks after surgery, patients receive oxaliplatin, leucovorin calcium, and fluorouracil(preoperative chemotherapy).Treatment repeats every 14 days for 6 courses in absence of disease progression or unacceptable toxicity.

Radiation: intensity-modulated radiation therapy; Drug: fluorouracil; Drug: oxaliplatin; Drug: leucovorin calcium; Procedure: therapeutic conventional surgery

Interventions

intensity-modulated radiation therapy RADIATION

Undergo IMRT

Also known as: IMRT

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

fluorouracil DRUG

Given IV

Also known as: 19893, 2,4-Dioxo-5-fluoropyrimidine,, 5-Fluoro-2,4(1H,3H)-pyrimidinedione,, Actino-Hermal, Adrucil, Arumel

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, 63121-00-6, [(1R,-2R)-1,2-cyclohexanediamine-N,N'], diaminocyclohexane, oxalatoplatinum, Dacotin, Dacplat

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

leucovorin calcium DRUG

Given IV

Also known as: 1492-18-8, 27275, 3590, 4292,, 5-formyl tetrahydrofolate, Adinepar, calcium (6S)-folinate, Calcifolin

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

therapeutic conventional surgery PROCEDURE

Undergo total mesorectal excision

Treatment(IMRT,fluorouracil,chemotherapy,surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically proven diagnosis of adenocarcinoma of the rectum (located below the peritoneal reflection or begins within 15 cm of the anal verge on flexible endoscopy) within 90 days of registration; diagnosis of rectal adenocarcinoma must be obtained by biopsy technique that does not completely excise the lesion (eg, fine needle aspiration, core needle biopsy)
• Clinically determined to be clinically staged (American Joint Committee on Cancer (AJCC) 7th edition \[ed.\]) T3-4 N0 M0 or T any N1-2 M0 based upon the following minimum diagnostic workup within 90 days prior to registration:
• Colonoscopy
• History/physical examination (including medication history screen for contraindications)
• Contrast-enhanced imaging of the abdomen and pelvis either by computed tomography (CT), magnetic resonance imaging (MRI), or whole body positron emission tomography (PET)-CT (preferred)
• Chest x-ray (or CT) of the chest to exclude distant metastases (except for those who have had whole body PET-CT per above bullet point)
• Transrectal ultrasound (TRUS) or MRI for T staging
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1,800 cells/mm\^3
• Platelets \>= 100,000 cells/mm\^3
• Hemoglobin \>= 8.0 g/dL (note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dL is acceptable)
• Aspartate aminotransferase (AST) \< 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase \< 2.5 x ULN
• Bilirubin =\< 1.5 ULN
• Calculated creatinine clearance (CrCl) \> 50 mL/min using Cockcroft-Gault formula

You may not qualify if:

• Prior radiotherapy to the region of the body that would result in overlap of RT fields with the current protocol treatment
• Severe, active comorbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days prior to registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol
• Evidence of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of treatment protocol or follow up
• Known, existing uncontrolled coagulopathy; subjects on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks
• Major surgery within 28 days of study enrollment (other than diverting colostomy)
• Crohn's disease or ulcerative colitis requiring hospitalization, surgery or immunosuppressive medications
• Prior allergic reaction to 5-Fluorouracil or oxaliplatin
• Any evidence of distant metastases (M1)
• Extension of malignant disease into the anal canal

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Fluorouracil; dehydroftorafur; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Emma C Fields, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 21, 2014
• Study Start: December 4, 2014
• Primary Completion: May 14, 2018
• Study Completion: May 13, 2021
• Last Updated: July 20, 2021

Record last verified: 2021-07

Locations

US (1)